title: A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish.
abstract: Members of the Slit family of secreted ligands interact with Roundabout (Robo) receptors to provide guidance cues for many cell types. For example, Slit/Robo signaling elicits repulsion of axons during neural development, whereas in endothelial cells this pathway inhibits or promotes angiogenesis depending on the cellular context. Here, we show that miR-218 is intronically encoded in slit2 and slit3 and that it suppresses Robo1 and Robo2 expression. Our data indicate that miR-218 and multiple Slit/Robo signaling components are required for heart tube formation in zebrafish and that this network modulates the previously unappreciated function of Vegf signaling in this process. These findings suggest a new paradigm for microRNA-based control of ligand-receptor interactions and provide evidence for a novel signaling pathway regulating vertebrate heart tube assembly.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA. jason.fish@utoronto.ca
authors.forename: Jason E
authors.initials: JE
authors.lastname: Fish
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Wythe
authors.forename: Tong
authors.initials: T
authors.lastname: Xiao
authors.forename: Benoit G
authors.initials: BG
authors.lastname: Bruneau
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
authors.forename: Stephanie
authors.initials: S
authors.lastname: Woo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000196:embryology*; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000502:physiology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D006023:Glycoproteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C120566:slit protein, vertebrate